Journal of Pakistan Association of Dermatologists. 2016;26 (3):177-181.

Original Article
Efficacy of intravenous glutathione vs. placebo for
skin tone lightening
Shazia Zubair*, Sajia Hafeez*, Ghulam Mujtaba**

* Dermatology Department, City Hospital, Multan

** Dermatology Department, Nishtar Medical College/ Nishtar Hospital, Multan

Abstract Objective To evaluate the efficacy and possible side effects of intravenous glutathione used for
lightening the skin tone.

Methods This placebo-controlled study was conducted in department of dermatology, City

Hospital, Multan from January 2014 to August 2015. Out of 50 enrolled patients 32 patients
completed the study. All patients were females with age ranging from 25 to 47 years. In group A, 8
patients had deranged liver function tests and one patient who developed anaphylactic shock were
excluded from study along with their controls from group B. Final results were concluded in only
those patients who completed the study. 32 patients were treated in two groups (A & B). In group A
16 patients were given intravenous glutathione and vitamin C. Patients in group B were given
intravenous normal saline as placebo. Taylor hyperpigmentation scale was used to measure the skin
tone. Two body sites, which were non-exposed to sun, were measured with Taylor
hyperpigmentation cards. Injection GSH Detox forte 1200 mg (aqua, glutathione 1200 mg, ascorbic
acid, hydrolyzed collagen 35 mg and sodium chloride) was given. Two injections per week for 6
weeks (total of 12 injections) were given. The effectiveness and side effects were assessed at the
end of therapy and 2 months, 4 months and 6 months after cessation of treatment.

Results After 12 injections of glutathione, 6 of 16 (37.5%) subjects showed significant

improvement, whereas 3 (18.7%) subjects improved with placebo (p = 0.054). After stopping the
treatment, this improvement was gradually lost and at six-month posttreatment follow-up only one
patient maintained this improvement. Adverse effects were noted in all subjects. Severe adverse
effects warranting discontinuation of treatment were deranged liver function tests (n=8) and patient
anaphylaxis (n=1).

Conclusion Glutathione is not very effective for skin tone lightening; moreover treatment loses its
efficacy with time. The side effects of the treatment are common.

Key words
Taylor hyperpigmentation scale, glutathione, anaphylaxis, skin tone.

Introduction complexion.1 Glutathione is a new tool in the

Desire for skin whitening among males and
females is increasing day by day. People are
using different drugs in topical, oral and
intravenous formulations to get the desired
Address for correspondence
Dr. Shazia Zubair,
Dermatology Department,
City Hospital, Multan
Email: mrsshaziazubair@yahoo.com
cosmetic industry. It is an antioxidant that is
naturally synthesized in the body.2 Glutathione is
also found in many foods like fresh uncooked
meat, dairy products and eggs.3 Oral absorption
is not reliable because of degradation by
enzymes in digestive tract.4 The proposed
mechanism of action of glutathione for skin
lightening is by direct inactivation of enzyme
tyrosinase, mediating the switch from eumelanin
to pheomelanin, quenching of free radicals and

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Journal of Pakistan Association of Dermatologists. 2016;26 (3):177-181.
peroxidase and modulation of depigmenting
abilities of melanocytotoxic agents.5-8
Glutathione is available in market as oral,
inhaled or topical formulations besides soaps
and intravenous injectables.9
Measuring the exact skin tone is a challenging
task. Different scientific devices are available
which can assess the index of melanin and
erythema.10,11 Most of them are very expensive
and require expertise to use. Taylor
hyperpigmentation score is an easy and
inexpensive way of measuring skin complexion.
It can measure from skin type I to skin type VI.12
More than 100 different skin hues can be
measured.
This study was undertaken to evaluate the
efficacy and safety of intravenous glutathione
for skin tone enhancement in Pakistani
population.
Methods
This placebo-controlled study was conducted in
department of dermatology, City Hospital,
Multan from January 2014 to august 2015. As
glutathione is not FDA approved, prior approval
of study was taken from the hospital ethical
committee. All patients were explained about the
possible side effects and written informed
consent was taken. Twenty-five healthy females,
aged 25 to 47 year willing to participate in the
study and pay for injection’s cost were enrolled
(group A). For every patient in group A, control
of same skin tone and age was kept in group B,
treated with placebo (normal saline). A thorough
physical examination of all patients was carried
out by a medical specialist. Complete blood
count and liver function tests were conducted
fortnightly. Exclusion criteria were age below 25
years, pregnancy and breast-feeding, personal or
family history of vitiligo, deranged liver
function tests and history of any skin or systemic
illness.
Skin tone was measured with Taylor
hyperpigmentation scale. Tylor
hyperpigmentation cards were used to measure
skin lightening from dark to light shades. Even
change of one shade is considered significant.
Two body sites, unexposed to sun, were chosen;
upper inner arm below the axilla and upper outer
thigh of all patients were noted with Taylor
hyperpigmentation cards. Measurements were
done by two independent observers.
Injection GSH Detox forte® 1200 mg (aqua,
glutathione 1200 mg, ascorbic acid, hydrolyzed
collagen 35 mg and sodium chloride) was given.
Two injections per week for 6 weeks with a total
of 12 injections were given. One 5ml injection
was diluted in 10ml distilled water. Butterfly
needle was used to give slow intravenous
injections over 30 minutes. Side effects were
noted during each injection session. Skin tone
assessment was done before starting treatment
after completing 12 injections and then 2
months, 4 months and 6 months after completing
injections.
Results
The initial study was conducted in 50 patients
(25 in group A treated with glutathione and 25 in
group B i.e. controls) but only 32 patients
completed the study. In group A, 8 patients had
deranged liver function tests and 1 patient
developed anaphylactic shock which were
excluded along with their controls from study.
Final results were evaluated in only those
patients who completed the study i.e. 16.
Table 1 shows the improvement in skin tone in
two groups. After 12 injections of glutathione, 6
of 16 subjects i.e. (37.5%) showed significant
improvement whereas 3 (18.7%) subjects
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noticed improvement in skin tone (p = 0.054). treatment, as well as, placebo had insignificant
When two groups were analyzed individually,
Table 1 Improvement of skin tone after completion of 12 injections of glutathione.
Follow-up duration after completion Group A (Glutathione) Group B (Placebo)
of treatment N=16 N=16
0 (after completing 12 injections) 6 (37.5%) 3 (18.7%)
2 months 3 (18.7%) 2 (12.5%)
4 months 3 (18.7%) 0
6 months 1 (6.2%) 0

Table 2 Side effects seen during glutathione treatment (n=25).

Side effect N (%)
Feeling of warmth during injection 11 (44)
Abdominal cramps 10 (40)
Deranged liver functions 8 (32)
Feeling of heart sinking 7 (28)
Diarrhea 4 (16)
Paresthesia 4 (16)
Dizziness 3 (12)
Anaphylactic shock 1 (4)
Vomiting 1 (4)

effect on skin tone (p = 0.895 and =0.998,
respectively). After stopping the treatment, this
improvement was gradually lost and at six-
month posttreatment follow-up only one patient
maintained this improvement.
Regarding side effects, all subjects in group A
(n=25) encountered side effects (Table 2). No
adverse effect was noted in any patient of group
B.
Discussion
In spite of much popularity, role of glutathione
in skin whitening has not been properly
evaluated. Search on Pubmed did not reveal any
study assessing the role of intravenous
glutathione in skin whitening, hence our results
could not be compared. Nonetheless, results of
our study challenge the skin lightening ability of
glutathione. After 12 injections of glutathione
administered in 6 weeks, only 6 (37.5%)
subjects noticed at least one level improvement
in their skin tone but similar to the placebo
group. This improvement was not sustainable
and six months after discontinuation of
treatment only one (6.2%) subject maintained
this result. Besides poor efficacy, the treatment
is also not cost-effective.
Theoretically, higher serum levels of glutathione
are achieved after intravenous administration;
nonetheless, it is also associated with higher
risks and side effects. Hence, glutathione has
been tried through other routes. Most of such
studies have emanated from South Asia.
Arjinpathana and Asawanonda1 in their double-
blind study compared oral glutathione 500mg
daily in two divided doses with placebo in 60
healthy medical students. The primary end point
of the study was reduction in melanin indices. At
4 weeks, they noticed a statistically significant
reduction in melanin indices in the study
population. Handog et al.4 used glutathione
lozenges in 30 Filipino females (skin type IV or
V) daily for 8 weeks. They noticed a significant
decrease in the melanin indices. No serious
clinical or laboratory adverse effects were seen.
In the double-blind study by Watanabe et al.13,
30 healthy adult women aged 30 to 50 years,
applied glutathione 2% (weight/weight) lotion to

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one side of the face and a placebo lotion to the
other side twice daily for 10 weeks. At week 10,
melanin indices were significantly lower on the
glutathione-treated side. No significant side
effects were observed with treatment. Why our
results were lower than those using the oral,
buccal and topical routes remains unanswered.
Different genetic background of study
population, the degree of sun exposure or
different tool of assessment may contribute to
lower results.
Safety of a new treatment modality is also a very
important factor. All patients in our study
experienced mild to severe adverse effects
ranging from minor palpitation to anaphylactic
shock and treatment had to be discontinued in 9
patients. This emphasizes that intravenous
glutathione treatment needs special settings
where anaphylaxis can be promptly managed.
Compared to intravenous route, drug used
through oral, buccal or cutaneous route is
relatively safe. As glutathione shifts melanin
synthesis pathway from eumelanin to
pheomelanin, this may increase the risk of sun-
induced malignancies, at least theoretically.14 As
glutathione is relatively newer treatment, its
long-term safety remains a problem. Moreover,
intravenous administration of very high doses of
a powerful antioxidant like glutathione might
subject the cells to potential risks of reductive
stress.14
In addition to its many recognized biological
functions, glutathione has skin lightening
ability.2 The role of glutathione as a skin
whitening was discovered as a side effect of
high doses of glutathione.15 Glutathione utilizes
different mechanisms to exert its action as skin
whitening agent at various levels of
melanogenesis.16 It inhibits melanin synthesis by
inhibiting L-DOPA to interact with tyrosinase in
the process of melanin production.2,3,5
Glutathione inhibits the production, as well as,
agglutination of melanin by interrupting the
function of L-DOPA.2,3 Glutathione also inhibits
melanin formation by direct inactivation of the
enzyme tyrosinase by binding and chelating
copper within the active site of enzyme.2
Antioxidant property of glutathione allows it to
inhibit melanin synthesis by quenching of free
radicals and peroxides that contribute to
activation of tyrosinase and formation of
melanin.3 Increases in glutathione level induce
the pigment cell to produce pheomelanin instead
of eumelanin.2 As a result, it is assumed that
depletion of glutathione would result in
eumelanin formation.2
Glutathione is an active ingredient in many
cosmetic preparations. Glutathione for skin
whitening is available in cream, soap, lotion,
nasal spray and injectable form.7,8 Topical
application of glutathione in the form of lotion is
not efficiently absorbed by the skin cells as the
thiol group undergoes rapid formation of
disulfide.9 Oral absorption of glutathione is
hydrolyzed by enzymes in the gastrointestinal
tract leading to its reduced bioavailability.9 The
level of glutathione increased in small amounts
temporarily when large oral doses were
administered.2,7 On the contrary, intravenous
glutathione delivers very high doses directly into
the systemic circulation and is the preferred
mode of administration.
Glutathione can be combined with vitamin C to
increase its absorption or N-acetyl cysteine to
boost its level.17
This study has important limitations. Blood
levels of glutathione could not be measured due
to unavailability of facility. Additionally,
assessment method of skin colour and tone in
this study was not an ideal one. Though the
Taylor hyperpigmentation score is used but it is
not a gold standard. Maxameter and other more
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Journal of Pakistan Association of Dermatologists. 2016;26 (3):177-181.
effective tools couldn’t be used due to financial
limitations.
Conclusion
Our study does not recommend glutathione for
skin lightening. Its safety as an intravenous drug
is also questioned. Further well-controlled trials
are required to evaluate glutathione efficiency as
skin lightening agent. Intravenous glutathione
administration should be carried out with more
sophistication and blood levels monitoring.
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